The overall objectives of this project is to gain a better understanding of the regulation of collagen metabolism during wound repair. Our ongoing studies are directed at identifying the factor(s) involved in human keloid formation; an example of altered collagen metabolism resulting in overhealing. Keloid IgG will be analyzed to determine if there is a specific antigen association which may indicate an immunologic etiology for keloids. Extracts of keloids and IgG associated protein will be studied for cell-mediated immune responses (CMI), leucocyte inhibitory factor (LIF), migration inhibitory factor (MIF) and lymphocyte blastogenesis activity. These fractions will also be tested with normal and keloid-derived fibroblasts for altered collagen synthesis activity. Finally, tissue typing studies will determine if there is an association between the HLA-DR locus antigens and keloid formation. Upon completion of all the above studies we should be able to identify if altered collage metabolism in keloid is secondary to an altered immune response. Ongoing studies of normal wound healing are directed at characterizing the interaction bwteen macrophages and fibroblasts and determining if macrophage factors regulate fibroblast proliferation, chemotaxis and collagen metabolism. We are also concerned with alterations in collagen metabolism and changes in the type of collagen synthesized in tissue under stress (striae and healing tendon) and the effects of steroids and beta-amino propionitrile on these processes.